Numerous medical devices have been applied for the treatment or alleviation of various diseases. Tribological issues widely exist in those medical devices and play vital roles in determining their performance and service life. In this review, the bio-tribological issues involved in commonly used medical devices are identified, including artificial joints, fracture fixation devices, skin-related devices, dental restoration devices, cardiovascular devices, and surgical instruments. The current understanding of the bio-tribological behavior and mechanism involved in those devices is summarized. Recent advances in the improvement of tribological properties are examined. Challenges and future developments for the prospective of bio-tribological performance are highlighted.